Related papers: Finding Multiple Reaction Pathways of Ligand Unbin…
We show that neural networks can be optimized to represent minimum energy paths as continuous functions, offering a flexible alternative to discrete path-search methods such as Nudged Elastic Band (NEB). Our approach parameterizes reaction…
The Minima Hopping global optimization method uses physically realizable molecular dynamics moves in combination with an energy feedback that guarantees the escape from any potential energy funnel. For the purpose of finding reactions…
Finding complex reaction and transformation pathways, involving many intermediate states, is in general not possible on the DFT level with existing simulation methods due to the very large number of required energy and force evaluations.…
Analyzing synthesis pathways for target molecules in a chemical reaction network annotated with information on the kinetics of individual reactions is an area of active study. This work presents a computational methodology for searching for…
We investigate the role of order/disorder transitions in alchemical simulations of protein-ligand absolute binding free energies. We show, in the context of a potential of mean force description, that for a benchmarking system (the complex…
We used various analytical and numerical techniques to elucidate signal propagation in a small enzymatic cascade which is subjected to external and internal noise. The nonlinear character of catalytic reactions, which underlie protein…
Due to the time scale problem, rare events are not accessible by straight forward molecular dynamics. The presence of multiple reaction channels complicates the problem even further. The feasibility of the standard free energy based methods…
The search for pathways that optimize the formation of a particular target molecule in a reaction network is a key problem in many settings, including reactor systems. Chemical reaction networks are mathematically well represented as…
The development of chemical reaction models aids understanding and prediction in areas ranging from biology to electrochemistry and combustion. A systematic approach to building reaction network models uses observational data not only to…
We present a molecular simulation method to simultaneously find multiple transition pathways, and their associated free-energy profiles. The scheme extends path-metadynamics (PMD) [Phys. Rev. Lett. 109, 020601 (2012)] with multiple paths…
Ligand unbinding is mediated by the free energy change, which has intertwined contributions from both energy and entropy. It is important but not easy to quantify their individual contributions. We model hydrophobic ligand unbinding for two…
The unbinding process of a protein-ligand complex of major biological interest was investigated by means of a computational approach at atomistic classical mechanical level. An energy minimisation-based technique was used to determine the…
A variety of natural phenomena comprises a huge number of competing reactions and short-lived intermediates. Any study of such processes requires the discovery and accurate modeling of their underlying reaction network. However, this task…
Ligand-receptor binding and unbinding are fundamental biomolecular processes and particularly essential to drug efficacy. Environmental water fluctuations, however, impact the corresponding thermodynamics and kinetics and thereby challenge…
We introduce a rigorous method to microscopically compute the observables which characterize the thermodynamics and kinetics of rare macromolecular transitions for which it is possible to identify a priori a slow reaction coordinate. In…
We propose an adaptive biasing algorithm aimed at enhancing the sampling of multimodal measures by Langevin dynamics. The underlying idea consists in generalizing the standard adaptive biasing force method commonly used in conjunction with…
We introduce a computational framework for generating realistic transition paths between distinct conformations of large bio-molecular systems. The method is built on a stochastic integro-differential formulation derived from the Langevin…
Large parallel gains in the development of both computational resources as well as sampling methods have now made it possible to simulate dissociation events in ligand-protein complexes with all--atom resolution. Such encouraging progress,…
Chemical reactions are often associated with an energy barrier along the reaction pathway which hinders the spontaneity of the reaction. Changing the energy barrier along the reaction pathway allows one to modulate the performance of a…
Atomistic modelling of phase transitions, chemical reactions, or other rare events that involve overcoming high free energy barriers usually entails prohibitively long simulation times. Introducing a bias potential as a function of an…